Association between the Presence of Autoantibodies Targeting Ficolin-3 and Active Nephritis in Patients with Systemic Lupus Erythematosus

Maëlle Plawecki, Elise Lheritier, Giovanna Clavarino, Noémie Jourde-Chiche, Saber Ouili, Stéphane Paul, Evelyne Gout, Françoise Sarrot-Reynauld, Nathalie Bardin, Pierre-Yves Boëlle, Laurent Chiche, Laurence Bouillet, Nicole M Thielens, Jean-Yves Cesbron, Chantal Dumestre-Pérard, Maëlle Plawecki, Elise Lheritier, Giovanna Clavarino, Noémie Jourde-Chiche, Saber Ouili, Stéphane Paul, Evelyne Gout, Françoise Sarrot-Reynauld, Nathalie Bardin, Pierre-Yves Boëlle, Laurent Chiche, Laurence Bouillet, Nicole M Thielens, Jean-Yves Cesbron, Chantal Dumestre-Pérard

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in the sera of some SLE patients, but their prevalence and significance have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-3 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE. In this retrospective study, sera from SLE patients (n = 165) were selected from a preexisting declared biological collection. Samples from healthy controls (n = 48) were matched with SLE sera. Disease activity was determined according to the SLEDAI score. Anti-ficolin-3, anti-dsDNA and anti-C1q antibodies levels were measured in sera by ELISA. First, a highly significant difference was found in the anti-ficolin-3 levels between SLE patients and healthy subjects. Anti-ficolin-3 antibodies were detected as positive in 56 of 165 (34%) SLE patients. The titer of anti-ficolin-3 antibodies was correlated with the SLEDAI score (r = 0.38, p<0.0001). The presence of anti-ficolin-3 antibodies was associated with anti-C1q and anti-dsDNA antibodies. Regarding associations with clinical manifestations, the presence of active lupus nephritis was significantly associated with the presence of anti-ficolin-3 antibodies (p≤0.001). This association with renal involvement was higher with anti-ficolin-3 or anti-C1q antibodies than with other auto-antibodies. Interestingly, the combination of anti-ficolin-3 and anti-C1q antibodies demonstrated higher specificity than any other serological biomarker. These results suggest that anti-ficolin-3 antibodies could be useful for the diagnosis of active nephritis in SLE patients.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Detection of anti-ficolin-3 antibodies in…
Fig 1. Detection of anti-ficolin-3 antibodies in patients with SLE.
A) Binding of anti-ficolin-3 antibodies to immobilized ficolin-3. Microtiter plates were coated with ficolin-3. Sera from SLE patients and healthy controls were added in serial dilutions. Results represent the mean +/- standard deviation. B) Anti-ficolin-3 antibodies in serum samples. Anti-ficolin-3 antibodies were measured in 48 samples from healthy controls and in 165 samples from patients with SLE. Horizontal lines in each group indicate the median values. Statistical analyses were performed by Mann-Whitney test. A, absorbance; AU, Arbitrary units.
Fig 2. Association between anti-ficolin-3 antibodies titers,…
Fig 2. Association between anti-ficolin-3 antibodies titers, biological markers and disease activity in patients with SLE.
Association between anti-ficolin-3 titers and anti-dsDNA antibodies (A), anti-C1q antibodies (B) and ficolin-3 concentrations (C) in SLE. D) Association between anti-ficolin-3 titers and SLE Disease Activity Index (SLEDAI). Statistical analyses were performed by Spearman’s rank correlation test.
Fig 3. Serum anti-ficolin-3 antibodies titers in…
Fig 3. Serum anti-ficolin-3 antibodies titers in SLE patients with active disease (flare) or in disease remission.
A) Anti-ficolin-3 titers in SLE patients with active disease (SLEDAI >4) (n = 77) or in disease remission (SLEDAI ≤4) (n = 88). B) Anti-ficolin-3 titers in SLE patients with active disease with renal involvement (n = 36) or without renal involvement (n = 41). Horizontal lines in each group indicate the median values. Statistical analyses were performed by Mann-Whitney test.

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